University of Lübeck receives optical microscope for intravital optical nanoscopy

German Research Foundation (DFG) grants 1.38 million Euros for high-resolution investigations of the blood-brain barrier in living organisms by intra vital STED microscopy – currently only three working groups in Europe work with such devices.

The University of Lübeck receives a unique microscope for high resolution images of living organisms. Applicant is Prof. Dr. Markus Schwaninger, Director of the Institute of Experimental and Clinical Pharmacology and Toxicology, together with Prof. Dr. Gereon Hüttmann from the Institute of Biomedical Optics and Prof. Dr. Peter König from the Institute of Anatomy.

The device, for which the German Research Foundation grants approx. 1.38 million Euros as part of the 'Novel experimental light microscopy for research' initiative, will be used to explore the blood-brain barrier in several projects. It is estimated that no more than a dozen of superresolution microscope, also known as a nanoscopes,  of this type are currently in use worldwide for imaging living organisms.

For physical reasons, a resolution of structures smaller than 0.2 micrometers (one micrometer or μm is one thousandth of a millimeter) is not directly possible with conventional light microscopy. However, the sizes of many biological structures, such as the blood-brain barrier, are in a much smaller range. By applying the stimulated emission effect, which was predicted by Einstein and also forms the basis of all lasers, it has been possible to overcome this resolution downwards. The physicist Stefan Hell was awarded the Nobel Prize in 2014 for the development of this microscopy technique, the "Stimulated Emission Depletion" (STED) microscope. In recent years, STED-based optical nanoscopy has not only been used to examine histological sections and cells, but also living organisms. The new nanoscope will continue along this path.

Structure and regulation of blood-brain barrier still largely not understood

The research project "Intravital nanoscopy for investigating the blood-brain barrier", for which the device will be provided, is dedicated to the investigation of the blood-brain barrier in living organisms. The blood-brain barrier is responsible for supplying the brain with nutrients and also ensures close communication between the brain and the rest of the body. Although the blood-brain barrier enables the normal function of the brain and is involved in the development of various diseases, its structure and regulation is still largely not understood.

The new microscope has two important properties for the project. Firstly, it allows the representation of very small structures in the blood brain barrier (approx. 0.08 μm resolution). In this way, the structure of the blood-brain barrier becomes visible. Secondly, it allows investigations in living organisms. This point will make it possible to investigate changes over time and regulation of the structures. The project will further optimize imaging in living organisms by active correction of image errors and other methods.

New technology will also be available to other research groups.

The new microscope is expected to go into operation in September 2019 at the University's Centre for Brain, Hormones and Behaviour (CBBM). The main users will be working groups of the Institute of Experimental and Clinical Pharmacology and Toxicology, the Institute of Biomedical Optics and the Institute of Anatomy. The new technology will also be available to other working groups on campus.

Superresolution microscopes are not yet widely used. In Lübeck, there has been no instrument so far. The next superresolution microscope is stationed in Hamburg. However, the Hamburg microscope, like most other microscopes of its type, does not offer the possibility to study living organisms. So far, only three research groups in Europe have succeeded in doing this.